Who\u27s your expert? Use of an expert opinion survey to inform development of American Psychiatric Association practice guidelines.

OBJECTIVE: For many clinical questions in psychiatry, high-quality evidence is lacking. Credible practice guidelines for such questions depend on transparent, reproducible, and valid methods for assessing expert opinion. The objective of this study was to develop and demonstrate the feasibility of a method for assessing expert opinion to aid in the development of practice guidelines by the American Psychiatric Association (APA). METHODS: A snowball process initially soliciting nominees from three sets of professional leaders was used to identify experts on a guideline topic (psychiatric evaluation). In a Web-based survey, the experts were asked to rate their level of agreement that specific assessments improve specific outcomes when they are included in an initial psychiatric evaluation. The experts were also asked about their own practice patterns with respect to the doing of the assessments. The main outcome measures are the following: number of nominated experts, number of experts who participated in the survey, and number and nature of quantitative and qualitative responses. RESULTS: The snowball process identified 1,738 experts, 784 (45 %) of whom participated in the opinion survey. Participants generally, but not always, agreed or strongly agreed that the assessments asked about would improve specified outcomes. Participants wrote 716 comments explaining why they might not typically include some assessments in an initial evaluation and 1,590 comments concerning other aspects of the topics under consideration. CONCLUSIONS: The snowball process based on initial solicitation of Psychiatry\u27s leaders produced a large expert panel. The Web-based survey systematically assessed the opinions of these experts on the utility of specific psychiatric assessments, providing useful information to substantiate opinion-based practice guidelines on how to conduct a psychiatric evaluation. The considerable engagement of respondents shows promise for using this methodology in developing future APA practice guidelines

Declining Clinical Course of Psychotic Disorders Over the Two Decades Following First Hospitalization: Evidence From the Suffolk County Mental Health Project

OBJECTIVE: Kraepelin considered declining course a hallmark of schizophrenia, but others have suggested that outcomes usually stabilize or improve after treatment initiation. The authors investigated this question in an epidemiologically defined cohort with psychotic disorders followed for 20 years after first hospitalization. METHOD: The Suffolk County Mental Health Project recruited first-admission patients with psychosis from all inpatient units of Suffolk County, New York (response rate, 72%). Participants were assessed in person six times over two decades; 373 completed the 20-year follow-up (68% of survivors); 175 had schizophrenia/schizoaffective disorder. Global Assessment of Functioning (GAF), psychotic symptoms, and mood symptoms were rated at each assessment. Month 6, when nearly all participants were discharged from the index hospitalization, was used as a reference. RESULTS: In the schizophrenia group, mean GAF scores declined from 49 at month 6 to 36 at year 20. Negative and positive symptoms also worsened (Cohen's d values, 0.45-0.73). Among participants without schizophrenia, GAF scores were higher initially (a mean of approximately 64) but declined by 9 points over the follow-up period. Worsening began between years 5 and 8. Neither aging nor changes in antipsychotic treatment accounted for the declines. In all disorders, depression improved and manic symptoms remained low across the 20 years. CONCLUSIONS: The authors found substantial symptom burden across disorders that increased with time and ultimately may undo initial treatment gains. Previous studies have suggested that better health care delivery models may preempt this decline. In the United States, these care needs are often not met, and addressing them is an urgent priority

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10−8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined

An Integrated Process for Co-Developing and Implementing Written and Computable Clinical Practice Guidelines

The goal of this article is to describe an integrated parallel process for the co-development of written and computable clinical practice guidelines (CPGs) to accelerate adoption and increase the impact of guideline recommendations in clinical practice. From February 2018 through December 2021, interdisciplinary work groups were formed after an initial Kaizen event and using expert consensus and available literature, produced a 12-phase integrated process (IP). The IP includes activities, resources, and iterative feedback loops for developing, implementing, disseminating, communicating, and evaluating CPGs. The IP incorporates guideline standards and informatics practices and clarifies how informaticians, implementers, health communicators, evaluators, and clinicians can help guideline developers throughout the development and implementation cycle to effectively co-develop written and computable guidelines. More efficient processes are essential to create actionable CPGs, disseminate and communicate recommendations to clinical end users, and evaluate CPG performance. Pilot testing is underway to determine how this IP expedites the implementation of CPGs into clinical practice and improves guideline uptake and health outcomes

Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations

Expression of 15-lipoxygenase-1 (ALOX15) in human Merkel cell carcinoma

Das Merkelzellkarzinom ist ein hoch maligner und aggressiv wachsender Hauttumor. Die Tumorinzidenz steigt mit dem Alter. Wird die Diagnose in einem frühen Tumorstadium (Stadium I, II) gestellt, sollte im Idealfall die weite Resektion des Primärtumors durchgeführt werden. Außerdem sollte, im Zuge der operativen Sanierung, eine Wächterlymphknotenbiopsie der regionären Lymphknotenstation angestrebt werden. Die vornehmlich lymphogene Metastasierung des Merkelzellkarzinoms wurde in der Literatur bereits hinreichend diskutiert. Frühere Studien weisen darauf hin, dass ALOX15 eine wichtige Rolle in der Karzinogenese und Metastasierung vieler Tumorarten spielt. In die Studie wurden alle Patienten die an der Medizinischen Universität Wien zwischen 1994 und 2014 wegen eines Merkelzellkarzinom behandelt wurden eingeschlossen. Die Primärtumor Proben von 46 Patienten wurden immunhistochemisch gefärbt und im Anschluss histologisch analysiert. Zur Färbung wurde 15-lipoxygenase-1 (ALOX15), Podoplanin (D2-40) und MCPyV large T-protein antibody herangezogen. In weiterer Folge wurden zwei Patientengruppen gebildet. Patienten welche keinerlei Metastasen entwickelten (T1, T2 N0 M0) wurden der Gruppe I zugeteilt (20/46, 43%). Wohingegen Patienten mit Lymphknoten Metastasen (jedes T N1 M0) und/oder Fernmetastasen (jedes T jedes N M1) der Gruppe II zugeteilt wurden (26/46, 57%). Die Tumorzell-Expression von ALOX15, Podoplanin und MCPyV wurde als positive bzw. negativ klassifiziert. Des weitern wurde histologisch in jeder Probe 3 Hotspots, mit einer Maximalanzahl von Lymphgefäßen identifiziert und die durchschnittliche Lymphgefäßdichte errechnet. 19/23 (83%) Primärtumor Proben exprimieren ALOX15. Darüberhinaus zeigten alle Merkelzellkarzinom Metastasen (17/17, 100%) ALOX15 Expression. Außerdem konnte gezeigt werden, dass Gruppe II Patienten (jedes T N1 M0; jedes T jedes N M1) verglichen mit Gruppe I Patienten (T1, T2 N0 M0) häufiger ALOX15 in ihren Primärtumoren exprimieren (11/12, 92% versus 8/11, 73%). Ausgehend von den vorliegenden Ergebnissen ist eine Hochregulation von ALOX15 in Merkelzellkarzinomen und deren Metastasen mit einem fortgeschritten Tumorstadium vergesellschaftet.Merkel cell carcinoma (MCC) is known to be a highly malignant and aggressive growing skin tumor. The tumor incidence increases with age. A diagnosis at an early stage (stage I, II) should lead to further surgical treatment (wide local excision of the primary tumor and nodal evaluation using sentinel lymph node biopsy). A retrospective medical chart review of 54 MCC patients treated at the Medical University of Vienna between 1994 and 2014 was conducted. Primary tumor samples of 46 MCC patients treated at our institution were immunostained for subsequent histological analysis. Samples were stained for 15-lipoxygenase-1 (ALOX15), Podoplanin (D2-40) and MCPyV large T-protein antibody. Two patient groups were established. Patients suffering from primary MCC without metastases (T1, T2 N0 M0) were allocated to Group I (20/46, 43%). Subjects diagnosed with regional lymph node metastases (any T N1 M0) and/or distant metastases (any T any N M1) were allocated to Group II (26/46, 57%). The tumor cell expression of ALOX15, Podoplanin and MCPyV was classified either positive or negative. Anti-D240 Antibody was used as a specific marker for lymphatic endothelium. For each sample, three hotspots with a maximum amount of lymphatic vessels were identified and the average lymphatic vessel density was determined. ALOX15 was expressed in 19/23 (83%) primary tumor samples and in all probes of metastases 17/17 (100%). ALOX15 was expressed more frequently among primary tumor samples of patients with regional lymph node metastases (any T N1 M0) and/or distant metastases (any T any N M1) compared to primary tumor probes of patients suffering from primary MCC without metastases (T1, T2 N0 M0) (11/12, 92% versus 8/11, 73%). Based on the results of the current investigation it appears likely that up-regulation of ALOX15 in primary MCC and metastasis is connected to an advanced stage disease.submitted by Alexandra FochtmannAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheWien, Med. Univ., Diss., 2015OeBB(VLID)171431

Disputatio XV.|| DE BAPTISMO || ALTERA,|| EX ARTICVLO AVGVSTANAE || Confessionis Nono.|| Cuius subiectas Propositiones,|| ... PRAESIDE AEGIDIO HUNNIO, S. Theologiae || Doctore & Professore, M. DANIEL FOCHT-||MANNVS STYRIVS die 27. Iulij in || Templo Arcis ... || tueri conabitur.||

Wittenberg, Univ., Theol. Disp., 1594Vorlageform des Erscheinungsvermerks: VVITEBERGAE || Excudebat Vidua Matthaei || VVelaci.|| ANNO M.D.XCIIII.|

Virtuti summae ac meritis splendissimis Viri ... Dn. Gebhardi ab Alvensleben ... : Cum Is. I. d. Mensis Octobr. MDCLXXXI. sub hor. Matut. Non sine ingenti bonorum omnium luctu humanis rebus exemptus fuisset. & Die XIV. Mensis Junii MDCLXXXII. Magna Principum, Baronum, Nobilium Coeterorumque Ordinum Pompa terrae solenniter mandaretur ... Hoc Monumentum erigere voluit Gebh. Joh. Fochtmannus LL. Studiosus

Text in lat. und dt